This proposal has two overall objectives. In a rat model of wound healing following carotid endarterectomy, the first objective is to explore the hypothesis that interactions between endothelial and smooth muscle cells are important in the control of endothelial and smooth muscle migration and proliferation and metabolism after arterial endothelial injury. The model irradiated carotid drying model) developed for this purpose depends on selective irradiation of carotid arterial segments and will, therefore, provide information on morphology and function of irradiated endothelial and smooth muscle cells in normal and injured arteries as well. The second objective is to explore the hypothesis that heparin is not only a pharmacological but an important biological endothelium-derived regulator of smooth muscle growth and metabolism in vivo. There are no quantitative data in vivo demonstrating endothelial cell modulation of smooth muscle cell function, migration and proliferation and vice versa; although heparin suppresses smooth muscle cell growth and might be synthesized by endothelial cells in vitro, there has been no demonstration in vivo of heparin synthesis by arterial endothelium and there are no data on the mechanism of heparin suppression of smooth muscle cell growth. The proposed studies will utilize light and electron microscopy, morphometry and measures of heparin and glycosaminoglycan synthesis.